Alcami recently authored an article featured in Drug Development & Delivery titled "A Practical Approach to Extractables & Leachables." 

INTRODUCTION

The study of extractables and leachables (E&L) has been evolving for many years. As pharmaceutical manufacturers, packaging vendors, and regulatory agencies gain more knowledge of extractable compounds, the scope of E&L guidelines grows with it. Many of the case studies that initiated interest in extractables and leachables are based on primary packaging. In some cases, the secondary or tertiary packaging were identified as sources of leachables. As a result, the primary emphasis of extractables screens has been on the packaging systems. The approach to these screens is well established. The first iterations of regulatory guidance addressed the common packaging materials in the United States Pharmacopeia (USP) chapter <661>, which relied heavily on physiochemical testing to characterize the material of construction but did not directly address extractables testing of the final packaging materials in detail. With advancements in the manufacture of plastics and increasing variety of base polymers used for packaging systems, it became evident that more specific guidelines are needed.

Agency expectations are quickly evolving for the evaluation of drug product packaging and delivery systems and the surfaces used during manufacture with respect to potential leachables. Every new and generic drug product must be assessed for extractables and leachables (E&L). In this top five list, Alcami experts will address the extractables and leachables questions our experts hear most.

1. What is the difference between an extractable and a leachable?
   Extractables are compounds that can be extracted from a packaging component, delivery system, or manufacturing surface via laboratory manipulation, such as exposure to solvents or heat. Extractables can be potential leachables. Leachables are compounds that passively migrate into the drug product over time, as a result of direct contact from the packaging system, in-use componentry, or a manufacturing surface.
   
   

Name: Matthew Collmeyer
Alcami Site: St. Louis, MO

How long have you been with Alcami?
I have been with Alcami since March 2018.

What is your role? 
I am the Sr. Manager of the Chemistry Laboratory Operations at Alcami's St. Louis, MO site.

What is the most rewarding part of your job?
The most rewarding part of my job is working with the chemistry team to tackle testing challenges and to see their dedication to ensuring we are doing as much as we can for our clients. Developing personnel through coaching and training is especially rewarding as well.

Your Manufacturing Milestones Matter.
Specialized to manufacture oral solid dose (OSD) forms, Alcami’s Wilmington, North Carolina site supports preclinical production through commercial launch and supply. Our cGMP manufacturing technologies, including low/high shear granulation and fluid bed drying capabilities, are arranged in flexible suites to support novel, advanced, and complex projects. 

In addition to OSD development and manufacturing, Alcami’s in-house analytical, stability, and packaging services provide an integrated and custom-tailored offering to help your product reach patients sooner.

In this two-part blog series, Alcami Senior Director of Global Manufacturing Science and Technology, Adam Kujath, discusses the market forecasts and the main manufacturing challenges involving highly potent APIs.

Read Part I: HPAPI Market Forecasts and Manufacturing Challenges

As demand for contract development and manufacturing of HPAPIs continues to increase from both new and existing relationships, it is important to anticipate and proactively expand to meet those needs. At Alcami, current market trends and our small molecule expertise drive our strategy to continue to invest in new capacity and expand our capabilities within this submarket.

The new elemental impurities regulations stress the importance of controlling all sources of elemental impurities in drug products. The regulations also impact all upcoming and current commercial drug products for human use. To comply with these regulations, it is critical to have an efficient, cost-effective, and agency-accepted approach.

Elemental impurities can contaminate or leach into a drug product from multiple sources (i.e. drug substance, excipients, water, equipment, and container closure systems), therefore, it is no longer acceptable to monitor the inlet raw materials only. A conservative risk-based approach is recommended, which should address all potential sources of elemental impurities. If it can be demonstrated that the elemental impurities present in the drug product are under control (less than the control threshold for three lots), then analysis at release is not needed. 

Name: Jasmine Mace
Alcami Site: Germantown, WI

How long have you been with Alcami?
I have been with Alcami since March 2014.

What is your role? 
I am an Analytical Scientist II.

What is the most rewarding part of your job?
It is very rewarding when I am presented with a difficult analytical method development and I find a way to deliver a solution to the client. Sometimes it takes some “thinking outside of the box” to arrive at a solution which satisfies the client’s needs for an analysis. The key for me is always asking the right questions:

• Is this testing needed, or are there adequate tests being done to satisfy the quality attributes of the process/compound?
• Are there any historical examples of how a similar problem was handled in the past?
• Which techniques could potentially be used?
• Did I think of what the test method could potentially affect downstream?

Alcami expanded its Science, Technology, Engineering, Arts, and Math (STEAM) education initiatives this fall with three specialized outreach events designed to encourage high school and college students to pursue careers in chemistry, engineering, and other STEAM fields. 

On October 30, 2018, Divine Savior Holy Angels High School (DSHA) students got a behind-the-scenes look at Alcami’s Germantown, Wisconsin active pharmaceutical ingredient (API) Center of Excellence, as part of the company’s ongoing efforts to promote women in STEAM careers. The all-girls engineering class toured the campus, met with key female company leaders, and learned about potential career paths through interactive presentations.

In this two-part blog series, Alcami Senior Director of Global Manufacturing Science and Technology, Adam Kujath, discusses the market forecasts and the main manufacturing challenges involving highly potent APIs.

The highly potent active pharmaceutical ingredient (HPAPI) market is one of the fastest growing CDMO submarkets, approaching a 9 percent compounded annual growth rate (CAGR). There is a continued industry focus on pipeline development oncology drugs, which by nature of indication is producing compounds that are increasingly potent.

In 2016, the not-for-profit Australian biopharmaceutical company Medicines Development for Global Health (MDGH) came to Alcami to initiate work on moxidectin, a novel new drug for the treatment of river blindness (onchocerciasis). The project utilized Alcami’s advanced analytical testing services and industry-leading accelerated turnaround time offering to meet critical New Drug Application (NDA) filing timelines. Now, the two companies are exploring new opportunities to help eliminate neglected tropical diseases that affect over 2 billion of the world’s most disadvantaged people.

Read this case study to learn more about how Alcami’s advanced analytical testing technology center supported MDGH's moxidectin’s US Food and Drug Administration (FDA) approval.